The prevalence, penetrance, and expressivity of etiologic <i>IRF6</i> variants in orofacial clefts patients from sub-Saharan Africa

BACKGROUND: Orofacial clefts are congenital malformations of the orofacial region, with a global incidence of one per 700 live births. Interferon Regulatory Factor 6 (IRF6) (OMIM:607199) gene has been associated with the etiology of both syndromic and nonsyndromic orofacial clefts. The aim of this study was to show evidence of potentially pathogenic variants in IRF6 in orofacial clefts cohorts from Africa. METHODS: We carried out Sanger Sequencing on DNA from 184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. We sequenced all the nine exons of IRF6 as well as the 5′ and 3′ untranslated regions. In our analyses pipeline, we used various bioinformatics tools to detect and describe the potentially etiologic variants. RESULTS: We observed that potentially etiologic exonic and splice site variants were nonrandomly distributed among the nine exons of IRF6, with 92% of these variants occurring in exons 4 and 7. Novel variants were also observed in both nonsyndromic orofacial clefts (p.Glu69Lys, p.Asn185Thr, c.175‐2A>C and c.1060+26C>T) and multiple congenital anomalies (p.Gly65Val, p.Lys320Asn and c.379+1G>T) patients. Our data also show evidence of compound heterozygotes that may modify phenotypes that emanate from IRF6 variants. CONCLUSIONS: This study demonstrates that exons 4 and 7 of IRF6 are mutational ‘hotspots’ in our cohort and that IRF6 mutants‐induced orofacial clefts may be prevalent in the Africa population, however, with variable penetrance and expressivity. These observations are relevant for detection of high‐risk families as well as genetic counseling. In conclusion, we have shown that there may be a need to combine both molecular and clinical evidence in the grouping of orofacial clefts into syndromic and nonsyndromic forms

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative

INTRODUCTION: Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. METHODS: in this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). RESULTS: Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6th and 7th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). CONCLUSION: A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.Scopu

Descriptive Epidemiology of Orofacial Clefts in Ethiopia

BACKGROUND: The prevalence of birth defects including orofacial clefts (OFC) in Ethiopia is not known and there is no established birth defects registration system. OBJECTIVES: To investigate the prevalence and incidence of OFC in Ethiopia. DESIGN: Retrospective hospital based descriptive study. METHODS: We obtained data from the Smile Train database on Ethiopian patients with OFC who underwent surgical treatment from June 2007 - December 2013 at 31 hospitals distributed throughout the country. Data related to live births in Ethiopia during the mentioned period was obtained from the Federal Ministry of Health database for estimates of the incidence and prevalence rates. RESULTS: The total number of life births during the study period was 18,811,316. During this same period, 18,073 cleft patients approximately ranging from 1 to 75 years old were examined and treated at the hospitals mentioned above. The incidence rate estimated from the total number of affected children during the study period (N=8232) is 0.44/1000 live births. The prevalence rate is 0.20/1000 and this was estimated using the number of total population in 2013 (N= 88,703,914). There is a significant difference in frequency between bilateral CLP (26.9%) versus unilateral CLP (73.1%) (P<0.0001). There is also a significant difference in frequency between bilateral cleft lips only (15.4%) versus unilateral cleft lip only (84.6%) P<0001. CONCLUSION: It is obvious that the findings in this study cannot be representative of the true picture but provides a previously unavailable national estimate of incidence and prevalence of orofacial clefts in Ethiopia. It can also be used as comparison for future community based studies

Oral Health-Related Quality of Life of Children Born With Orofacial Clefts in Ethiopia and Their Parents

Objective: To assess the oral health–related quality of life (OH-RQoL) using a translated standardized measure in an understudied population of Ethiopian children born with orofacial clefts (OFCs) and their parents. Methods: Using a descriptive study design, we assessed the OH-RQoL of 41 patients with OFCs between the ages of 8 and 17 years and their parents. Participants received multidisciplinary cleft care from 2008 to 2016. They completed an Amharic translation of the Child Oral Health Impact Profile (COHIP). Results: There was strong internal reliability with the translated COHIP for parents and patients. Parents’ COHIP scores ranged from 67 to 186, and patients’ scores were 78 to 190. The mean for patients and parents was 155, indicating good OH-RQoL. Conclusion: The Amharic translation of the COHIP appears appropriate for use with families in Ethiopia. Both parents and patients reported OH-RQoL at similar levels as other international populations. </jats:sec

Study of Nabhi Pradesha and Nabhi Nadi Shareera

Ayurveda is an intricate and detailed science, which provides great insight into the importance of every part of the body. One of the most important parts is Nabhi along with other structures. The Nabhi plays the most important role in the development of the body from the very beginning of the life, even at embryonic stage. In Ayurveda, Nabhi is believed to be the root of Siras present between Pakvashaya and Amashaya. Such Siras are passage ways of nutrients and serve as outlets for showering sustenance in different parts of our body. Due to Nabhi’s importance, many Ayurveda Acharya’s found Nabhi to be a significant structure in the body and core of all organs of the body. In ancient Indian tradition the navel of the god Vishnu is consider as the centre of the universe at the source of the life. From his navel, a new world emerges. It also has aesthetic importance but also tells the health status, it is a site of various treatment to which makes it worthy to consider its anatomical concepts and applied aspects. In embryonic stage Nabhi place an important role in the development of fetus, by the formation of Garbha Nabhi Nadi through which nutrient materials exchange between mother and fetus this will explains the concepts of Garbha Phoshana and Garbha Matru-Paratantrata concepts. With this background an attempt is done for the literary study of Nabhi Pradesha and Nabhi Nadi Shareera

Study on concept of Guda Pradesha w.s.r. to Guda Valis

The anatomical knowledge of Guda (anal canal) and its relations are Very important to discuss about anal diseases. Guda is defined as the opening where the Gastro intestinal tract ends, and exits the body which excretes faeces and flatus through it. It is Moola of Pureeshavahasrotas. Charaka described it is one among the fifteen Kostangas, and Recognised two parts in it ie. Uttara Guda and Adhara Guda It is one among nine Bahirmukha Srotas located in pelvic region. Guda gets forming along with other body Parts as early as in the fourth month and fully formed by seventh month of gestation. Embryologically it is derived from Matrujabhava. According to Sushruta Pureeshadhara Kala is related to Guda and it is Moola of Pureeshavaha Srotas, and also is Sadhyopranahara Marma. According to Amarakosha Guda has synonyms like Apanam and Payu

Multidisciplinary approach to genomics research in Africa:the AfriCRAN model

This article is an outcome of the African Craniofacial Anomalies Research Network (AfriCRAN) Human Hereditary and Health (H3A) grant planning meeting in 2012 in Lagos, Nigeria. It describes the strengths of a multidisciplinary team approach to solving complex genetic traits in the craniofacial region. It also highlights the different components and argues for the composition of similar teams to fast track the discovery of disease genes, diagnostic tools, improved clinical treatment and ultimately prevention of disease

Novel <i>IRF6 </i>mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub-Saharan Africa

Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice-site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6-related VWS and PPS in sub-Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high-risk families

Review on Utpatti of Shukra Dhatu as per Ayurveda

Shukra Dhatu is present throughout the body, but according to Sushruta, it is most prominent at the Bladder opening. Moola-Sthana (origin) of Shukravaha Srotasa (system related with reproductive tissue) has Been attributed to Vrishana (testis), Shepha (penis), Stana (breast), and Majja (bone marrow). Shukradhara Kala is a vital structure that spans the entire body. Shukra Pramaana is Ardha Anjali (1/2 handful), whereas typical semen volume is 2 ml according to WHO standards. Dhairya (sexual potency), Chyavanam (timely ejaculation), Preeti (love for partner), Dehabalam (physical strength), Harshana (sexual desire), and Beejaratha (to fulfil the purpose of Beeja, i.e., procreation) are considered to be the functions of the Shukra. When Shukra, which is prevalent throughout the body, is triggered by Harsha, Darshana, Smarana, hearing the voice, Sparshana, or performing sexual activities, Shukra travels to the testis and ejaculates it. Spermatogenesis is a highly structured, complicated series of mitotic and meiotic differentiation Processes that result in genetically differentiated male gametes for fertilisation with the female ovum. It aids in the propagation of a species and adds to genetic diversity on a larger scale. Spermatogenesis is the process of turning spermatogonial germ cells into spermatids through cell proliferation and remodelling. Several Inherent and external variables influence the process. Spermatozoa are discharged into the Epididymis via the seminiferous tubules, where they undergo post-testicular maturation and storage. At the time of ejaculation, the ejaculate, or semen, is freshly generated. Ejaculation usually follows a predictable Pattern

Novel <i>GREM1 </i>Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate

Objective: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. Patients and Method: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. Results: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. Conclusion: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P. </jats:sec